In solid-phase synthesis, a universal linker modified on a solid support is generally used for the synthesis of oligonucleotides bearing a non-natural nucleoside at the 3′-terminus. Herein, we have developed three new universal linkers using bicyclo[2.2.2]octane-2,3-diol group. Saturated, unsaturated, and dibenzo-fused type linkers containing bicyclo[2.2.2]octane-2,3-diol, bicyclo[2.2.2]oct-5-ene-2,3-diol, and 9,10-dihydro-9,10-ethanoanthracene-11,12-diol, respectively, were synthesized and loaded onto a solid support. Upon releasing the oligonucleotides from the solid supports under basic conditions, it was found that the desired oligonucleotides and the impurities derived from the universal linker were well-separable on the HPLC chart using the dibenzo-fused type linker. In the synthesis of the phosphorothioate-modified oligonucleotide, the dibenzo-fused type also showed that the desired oligonucleotide and the impurities were well-separable. These results demonstrated that the dibenzo-fused type linker has great potential to become a new universal linker used for the solid-phase synthesis of oligonucleotides.

在固相合成中，在固相载体上修饰的通用接头通常用于合成在 3'-末端带有非天然核苷的寡核苷酸。在此，我们开发了三种使用双环 [2.2.2] 辛烷-2,3-二醇基团的新型通用接头。含有双环[2.2.2]辛烷-2,3-二醇、双环[2.2.2]辛-5-烯-2,3-二醇和9,10-二氢-二醇的饱和、不饱和和二苯并稠合型接头分别合成了 9,10-ethanoanthracene-11,12-diol 并加载到固体载体上。在碱性条件下从固体支持物上释放寡核苷酸后，发现所需的寡核苷酸和来自通用接头的杂质在使用二苯并稠合型接头的 HPLC 图上可很好地分离。在硫代磷酸酯修饰的寡核苷酸的合成中，二苯并融合型还表明所需的寡核苷酸和杂质可以很好地分离。这些结果表明，二苯并融合型接头具有成为用于寡核苷酸固相合成的新型通用接头的巨大潜力。